title: Economic analysis of bevacizumab, cetuximab, and panitumumab with fluoropyrimidine-based chemotherapy in the first-line treatment of KRAS wild-type metastatic colorectal cancer (mCRC).
abstract: OBJECTIVE
  Colorectal cancer (CRC) is the third most commonly diagnosed cancer in Canada (excluding non-melanoma skin cancers). Bevacizumab is a recombinant humanized monoclonal antibody that selectively binds to human vascular endothelial growth factor. A sub-study confirmed its effectiveness in KRAS wild-type patients. Recent evidence has shown clinical benefit from anti-epidermal growth factor treatments cetuximab and panitumumab in these patients. The cost-effectiveness, to the Canadian healthcare system, of fluoropyrimidine-based chemotherapy (FBC) in combination with bevacizumab, cetuximab, or panitumumab was assessed for first-line treatment of KRAS wild-type mCRC patients.
  
  
  METHODS
  A Markov model was developed and calibrated to progression-free/overall survival, using separately reported trial survival and adverse event results for each comparator. Health-state resource utilization was derived from published data and oncologist input. Utilities and unit prices were obtained from published literature and standard Canadian sources.
  
  
  RESULTS
  Results per patient are over a lifetime horizon, to a maximum of 10 years, with 5% annual discounting. Comparators are ordered by total cost and the incremental cost-effectiveness ratio (ICER) of each is determined against the previous non-dominated therapy. Compared to FBC alone, bevacizumab + FBC has an ICER of $131,600 per QALY gained. Compared to bevacizumab + FBC, panitumumab + FBC is dominated and cetuximab + FBC has an ICER of $3.8 million per QALY. In probabilistic sensitivity analysis, bevacizumab + FBC had ∼100%, ∼100%, and 98.9% probabilities of being more cost-effective than both of the other combination treatments at thresholds of $50,000/QALY, $100,000/QALY, and $200,000/QALY, respectively.
  
  
  CONCLUSIONS
  For first-line treatment of KRAS-WT mCRC, bevacizumab + FBC is associated with substantially lower costs as compared to panitumumab + FBC or cetuximab + FBC. Key limitations were that survival curves and adverse event rates were taken from separate clinical trials and that an indirect comparison was not included. Given these findings, bevacizumab is likely to offer the best value for money for this patient population.
authors.affiliation: OptumInsight, Burlington , ON , Canada.
authors.forename: Donna
authors.initials: D
authors.lastname: Lawrence
authors.forename: Michael
authors.initials: M
authors.lastname: Maschio
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Leahy
authors.forename: Simon
authors.initials: S
authors.lastname: Yunger
authors.forename: Jacob C
authors.initials: JC
authors.lastname: Easaw
authors.forename: Milton C
authors.initials: MC
authors.lastname: Weinstein
mesh_terms: D020533:Angiogenesis Inhibitors / Q000191:economics*; D000911:Antibodies, Monoclonal / Q000191:economics*; D061067:Antibodies, Monoclonal, Humanized / Q000191:economics*; D000970:Antineoplastic Agents / Q000191:economics*; D000068258:Bevacizumab; D002170:Canada; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000191:economics* / Q000235:genetics / Q000473:pathology; D017281:Cost of Illness; D003362:Cost-Benefit Analysis; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000191:economics; D005260:Female; D006801:Humans; D008297:Male; D008390:Markov Chains; D008875:Middle Aged; D018803:Models, Economic; D000077544:Panitumumab; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D019057:Quality-Adjusted Life Years; D018631:ras Proteins
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D000068258:Bevacizumab; D000077544:Panitumumab; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab